title: Kir4.1 channel expression is essential for parietal cell control of acid secretion.
abstract: Kir4.1 channels were found to colocalize with the H(+)/K(+)-ATPase throughout the parietal cell (PC) acid secretory cycle. This study was undertaken to explore their functional role. Acid secretory rates, electrophysiological parameters, PC ultrastructure, and gene and protein expression were determined in gastric mucosae of 7-8-day-old Kir4.1-deficient mice and WT littermates. Kir4.1(-/-) mucosa secreted significantly more acid and initiated secretion significantly faster than WT mucosa. No change in PC number but a relative up-regulation of H(+)/K(+)-ATPase gene and protein expression (but not of other PC ion transporters) was observed. Electron microscopy revealed fully fused canalicular membranes and a lack of tubulovesicles in resting state Kir4.1(-/-) PCs, suggesting that Kir4.1 ablation may also interfere with tubulovesicle endocytosis. The role of this inward rectifier in the PC apical membrane may therefore be to balance between K(+) loss via KCNQ1/KCNE2 and K(+) reabsorption by the slow turnover of the H(+)/K(+)-ATPase, with consequences for K(+) reabsorption, inhibition of acid secretion, and membrane recycling. Our results demonstrate that Kir4.1 channels are involved in the control of acid secretion and suggest that they may also affect secretory membrane recycling.
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Penghong
authors.initials: P
authors.lastname: Song
authors.forename: Stephanie
authors.initials: S
authors.lastname: Groos
authors.forename: Brigitte
authors.initials: B
authors.lastname: Riederer
authors.forename: Zhe
authors.initials: Z
authors.lastname: Feng
authors.forename: Anja
authors.initials: A
authors.lastname: Krabbenhöft
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Adam
authors.initials: A
authors.lastname: Smolka
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Hagen
authors.forename: Clemens
authors.initials: C
authors.lastname: Neusch
authors.forename: Ursula
authors.initials: U
authors.lastname: Seidler
mesh_terms: D000818:Animals; D001692:Biological Transport; D004594:Electrophysiology / Q000379:methods; D004705:Endocytosis; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D005786:Gene Expression Regulation; D017506:H(+)-K(+)-Exchanging ATPase / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D010295:Parietal Cells, Gastric / Q000166:cytology*; D011188:Potassium / Q000737:chemistry; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis / Q000502:physiology*; D000098854:Kcnj10 Channel
chemical_list: D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D017506:H(+)-K(+)-Exchanging ATPase; D011188:Potassium